Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active‐controlled, randomized, double‐blind study with open‐label extension (the EVERGREEN study)

Abstract

Aim To investigate the efficacy and safety of evogliptin compared to linagliptin in patients with type 2 diabetes mellitus (T2DM). Materials and methods In this 12‐week multicenter, randomized, double‐blind, active‐controlled, and 12‐week open‐label extension study, a total of 207 patients with T2DM who had HbA1c levels of 7.0–10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). Results After 12 weeks of treatment, the mean changes in HbA1c in the evogliptin group and the linagliptin group were − 0.85% and − 0.75%, respectively. The between‐group difference was −0.10% (95% CI: −0.32 to 0.11), demonstrating non‐inferiority based on a non‐inferiority margin of 0.4%. The change in MAGE was −24.6 mg/dL in the evogliptin group and − 16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by −0.94%, with HbA1c values <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks. Conclusion In this study, the glucose‐lowering efficacy of evogliptin was non‐inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycemic variability without causing any serious adverse events in patients with T2DM.